Outcomes among newborns with total serum bilirubin levels of 25 mg per deciliter or more

N Engl J Med. 2006 May 4;354(18):1889-900. doi: 10.1056/NEJMoa054244.


Background: The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined.

Methods: We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 micromol per liter) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants born from 1995 through 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires, and neurodevelopmental evaluations that had been performed in a blinded fashion.

Results: Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 micromol per liter) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 micromol per liter) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in 5. Follow-up data to the age of at least two years were available for 132 of 140 children with a history of hyperbilirubinemia (94 percent) and 372 of 419 controls (89 percent) and included formal evaluation at a mean (+/-SD) age of 5.1+/-0.12 years for 82 children (59 percent) and 168 children (40 percent), respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95 percent confidence intervals excluded a 3-point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17 percent) had "questionable" or abnormal findings on neurologic examination, as compared with 48 controls (29 percent; P=0.05; adjusted odds ratio, 0.47; 95 percent confidence interval, 0.23 to 0.98; P=0.04). The frequencies of parental concern and reported behavioral problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioral problems.

Conclusions: When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bilirubin / blood*
  • Case-Control Studies
  • Child Development*
  • Cohort Studies
  • Combined Modality Therapy
  • Exchange Transfusion, Whole Blood*
  • Female
  • Gestational Age
  • Humans
  • Hyperbilirubinemia, Neonatal / blood
  • Hyperbilirubinemia, Neonatal / psychology
  • Hyperbilirubinemia, Neonatal / therapy*
  • Infant, Newborn
  • Intelligence
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Neurologic Examination
  • Outcome Assessment, Health Care
  • Phototherapy*
  • Single-Blind Method
  • Socioeconomic Factors
  • Surveys and Questionnaires


  • Bilirubin